Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
Primary Ciliary Dyskinesia
About this trial
This is an interventional basic science trial for Primary Ciliary Dyskinesia focused on measuring Mucociliary clearance, Radial Spoke Head Component 1 (RSPH1), Dynein Axonemal Heavy Chain 5 (DNAH5), albuterol, short acting beta-adrenergic (SABA), SABA
Eligibility Criteria
Inclusion Criteria for PCD Patients
- Confirmed PCD diagnosis with identified genetic mutations
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
- Forced Expiratory Volume (FEV1) of at least 30 percent of predicted
Inclusion Criteria for Healthy Controls:
- Age ≥ 18 years old
- Subjects must have an FVC, FEV1 and FVC/FEV1 of at least 80% of predicted. Subjects who fall out of the normal range will be offered a copy of the test to share with their personal physician.
- No pre-existing lung disease (asthma, cystic fibrosis, etc.).
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy.
Exclusion Criteria:
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, immunodeficiency, history of tuberculosis
- Any acute infection requiring antibiotics within 4 weeks of study.
- Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
- Medications which may impact the results of the study treatment, or may interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents)
- Active smoking to include e-cigarettes within 1 year of the study, or lifetime of > 10 pack years of smoking
- History of vaping or current vaping.
- Viral upper respiratory tract infection within 4 weeks of challenge.
- Radiation exposure history in the past year which would be outside the safe levels
- Pregnant or lactating women will also be excluded since the risks associated with radiation are unknown and cannot be justified
Use of the following medications:
- Use of beta blocking medications
- Receipt of LAIV (Live Attenuated Influenza Vaccine), also known as FluMist , within the prior 30 days, or any vaccine within the prior 5 days
- Multivitamins, Vitamin C or E or herbal medications in the 4 days prior to the treatment visit
- Non-steroidal anti-inflammatory drugs in the 4 days prior to the treatment visit.
- Allergy/sensitivity to study drugs or their formulations:
- Known Immunoglobulin E (IgE) mediated hypersensitivity to albuterol
Physical/laboratory indications:
- Temperature > 37.8 degrees Celsius (C)
- Subjects >15 years- Systolic BP >150 mm hg or < 90 mm Hg or diastolic BP> 90 mm Hg or < 50 and Subjects 12-15 years - Systolic BP > 130 mmHg or < 80 mmHg or diastolic BP > 80 or <40
- Oxygen saturation of < 93 percent
- Inability or unwillingness of a participant to give written informed consent.
Sites / Locations
- University of North Carolina Chapel HillRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Active Comparator
Active Comparator
Genotypes associated mild phenotype
Genotypes associated with severe phenotype
Healthy Control
Subjects with 2 confirmed mutations in RSPH1, Radial Spoke Head Component 9 (RSPH9), Radial Spoke Head Component 4A (RSPH4a), or Dynein Axonemal Heavy Chain 11 (DNAH11). This group may also include subjects with mutations in newly identified genes that are associated with a milder clinical phenotype.
Subjects with 2 confirmed mutations in DNAH5, Dynein Axonemal Intermediate Chain 1 (DNAI1), Coiled-Coil Domain Containing 39 (CCDC39), or Coiled-Coil Domain Containing 40 (CCDC40). This group may also include subjects with mutations in newly identified genes that are associated with a more severe clinical phenotype.
Healthy subjects with no pre-existing lung disease.